Study of ovarian Angiogenesis in Polycystic Ovary Syndrome (PCOS): Role of VEGF and Angiopoietins in a DHEA rat model

ABRAMOVICH DALHIA

Woods Hole

Simposio; Frontiers in Reproduction Symposium; 2013

Vascular endothelial growth factor (VEGF) is the main player in angiogenesis. However, the development of mature vascular network requires the action of a variety of factors, e.g. the angiopoietins (ANGPTs). ANGPT1 is necessary for the recruitment of perivascular cells that lead to stabilization of newly developed capillaries. PCOS is the most common endocrinological pathology among women of reproductive age. It is characterized by chronic anovulation, oligo- or amenorrhea, hyperandrogenism, obesity, insulin resistance, hypersecretion of androgens by ovarian stroma and theca cells and the presence of multiple cysts. PCOS patients present elevated levels of VEGF in serum and follicular fluid. Objectives: 1) To examine the ovarian expression of VEFG, ANGPTs and their receptors, FLK1 and TIE2 respectively, in a rat model of dehydroepiandrosterone (DHEA)-induced PCOS. 2) To analyze the effect of ovarian VEGF inhibition on ANGPT/TIE2, follicular development and vascular stability in said model. 3) To examine the levels of ANGPT1 and soluble TIE2 in follicular fluid from PCOS and control patients. Results: VEGF levels were increased in the PCOS ovaries, whereas the levels of its receptor FLK1 were decreased. In addition, the periendothelial cell area and the ANGPT1/ANGPT2 ratio in the ovary were increased in the PCOS group. ANGPT1 levels were also increased in human follicular fluid from PCOS patients. In the rat model, percentage of primary follicles was increased and the percentage of preantral follicles and corpora lutea was decreased in the PCOS group. VEGF inhibition decreased the percentage of primary follicles close to control values. In addition, cyst percentage was lower than the PCOS group without treatment. Discussion: We have found an alteration in the ANGPT/TIE2 system in a DHEA-induced PCOS rat model, which would lead to an increase in periendothelial cell recruitment. This alteration is also observed in PCOS patients. Ovarian VEGF inhibition can partially restore the accumulation of small follicles in PCOS rats and reduces cyst formation, improving ovulation and follicular development. Therefore, the inhibition of VEGF could be considered as a new strategy to restore ovarian function in PCOS patients.